DHEAS and cortisol/DHEAS-ratio in recurrent depression: State, or trait predicting 10-year recurrence?

Mocking, R. J. T., Pellikaan, C. M., Lok, A., Assies, J., Ruhe, H. G., Koeter, M. W., Visser, I., Bockting, C. L., Olff, M. & Schene, A. H., Sep-2015, In : Psychoneuroendocrinology. 59, p. 91-101 11 p.

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  • DHEAS and cortisol-DHEAS-ratio in recurrent depression

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  • R. J. T. Mocking
  • C. M. Pellikaan
  • A. Lok
  • J. Assies
  • H. G. Ruhe
  • M. W. Koeter
  • I. Visser
  • C. L. Bockting
  • M. Olff
  • A. H. Schene

Background: Major depressive disorder (MDD) has been associated with low dehydroepiandrosterone-sulphate (DHEAS), - particularly relative to high cortisol - although conflicting findings exist. Moreover, it is unclear whether low DHEAS is only present during the depressive state, or manifests as a trait that may reflect vulnerability for recurrence. Therefore, we longitudinally tested whether low DHEAS and high cortisol/DHEAS-ratio in recurrent MDD (I) reflects a trait, and/or (II) varies with depressive state. In addition, we tested associations with (III) previous MOD-episodes, (IV) prospective recurrence, and (V) effects of cognitive therapy.

Methods: At study-entry, we cross-sectionally compared morning and evening salivary DHEAS and molar cortisol/DHEAS-ratio of 187 remitted recurrent MDD-patients with 72 matched controls. Subsequently, patients participated in an 8-week randomized controlled cognitive therapy trial. We repeated salivary measures after 3 months and 2 years. We measured clinical symptoms during a 10-year follow-up.

Results: Remitted patients showed steeper diurnal DHEAS-decline (p <.005) and a flatter diurnal profile of cortisol/DHEAS-ratio (p <.001) than controls. We found no state-effect in DHEAS or cortisol/DHEAS-ratio throughout follow-up and no association with number of previous episodes. Higher morning cortisol/DHEAS-ratio predicted shorter time till recurrence over the 10-year follow-up in interaction with the effects of cognitive therapy (p <.05). Finally, cognitive therapy did not influence DHEAS or cortisol/DHEAS-ratio.

Conclusions: Diurnal profiles of DHEAS and cortisol/DHEAS-ratio remain equally altered in between depressive episodes, and may predict future recurrence. This suggests they represent an endophenotypic vulnerability trait rather than a state-effect, which provides a new road to understand recurrent depression and its prevention. (C) 2015 Elsevier Ltd. All rights reserved.

Original languageEnglish
Pages (from-to)91-101
Number of pages11
Publication statusPublished - Sep-2015


  • Hypothalamic-pituitary-adrenal (HPA) axis, Major depressive disorder (MDD), Dehydroepiandrosterone-sulphate (DHEAS), Cortisol, Remission, Recurrence, MAJOR DEPRESSION, DEHYDROEPIANDROSTERONE-SULFATE, PLASMA-CONCENTRATIONS, SALIVARY CORTISOL, COGNITIVE THERAPY, STRESS, DISORDER, BRAIN, PSYCHOTHERAPY, ADOLESCENTS

ID: 23499207